We will try to improve the chemical and biological properties of trans-N,N,N,N-tetrapropyl-1,2-cyclohexanedioxydiacetamide (47-PR), one of our most promising calcium ionophores to date. This molecule shows coronary vasodilation effects in rabbit atrium, hyperpolarization of membrane potential of canine Purkinje fibers as well as other physiological effects of cardiovascular interest. It is a neutral, liquid, ionophore which binds calcium greater than strontium greater than barium in the range of 10 to the 4th power to 10 to the 5th power in methanol. Binding in water is known to be much weaker. We hope to increase the binding strength of the system at least ten-fold, possibly improve its selectivity for calcium over other cations, and have a solid form available. These goals may be realized by adding carboxy binding sites either directly on the cyclohexane ring or at the end of a long polymethylene chain which can be designed for maximum interaction with the other binding sites. Such carboxy ligands may more closely approximate the behavior found for the naturally occurring carboxy ionophores such as X-537A which has great cardiovascular potential. Variation of structure leading to sodium selectivity will also be explored since both sodium and calcium transport are important in cardiovascular events. BIBLIOGRAPHIC REFERENCES: I.J. Borowitz, W.O. Lin, T.C. Wun, R. Bittman, L. Weiss, V. Diakiw, and G.B. Borowitz, "The Preparation and Properties of Neutral Diamide ionophores for Group IIA Metal Cations", Tetrahedron, in press, 1977. T.C. Wun, R. Bittman and I.J. Borowitz, "Binding Properties of Neutral Diamide Ligands for Alkaline-Earth Cations", Biochemistry, in press, 1977.